Bedaquiline was described for the first time in 2004 at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting, after the drug had been in development for over seven years.[8]

One of the first published trials of Bedaquiline was a Phase II trial of 47 patients, which showed that the drug was effective in reducing the time to TB-free sputum cultures.[9] A subsequent phase II efficacy trial was published in 2010 and sponsored by Tibotec and the TB Alliance.[10]

It is manufactured by Johnson & Johnson (J&J), who sought accelerated approval of the drug, a type of temporary approval for diseases lacking other viable treatment options.[11] By gaining approval for a drug that treats a neglected disease, J&J is now able to request expedited FDA review of a future drug.[12]

There is some controversy over the approval for the drug, as the FDA's ruling was based on a surrogate outcome (sputum cultures) as opposed to patient deaths. In the clinical trials used for approval, the patients taking bedaquiline were more likely to die (a rate of death of 11.4% in the treatment group, compared to 2.5% in the control group[13]), even though they had resolution of TB based on sputum cultures.[14]

Bedaquiline should not be co-administered with other drugs that are strong inducers or inhibitors of CYP3A4, the hepatic enzyme responsible for oxidative metabolism of the drug.[15] Co-administration with rifampin, a strong CYP3A4 inducer, results in a 52% decrease in the AUC of the drug. This reduces the exposure of the body to the drug and decreases the antibacterial effect. Co-administration with ketoconazole, a strong CYP3A4 inhibitor, results in a 22% increase in the AUC, and potentially an increase in the rate of adverse effects experienced[15]